Figure 3.

Pseudogene RNA exists in various forms and plays a vital role in target gene expression. A pseudogene can be transcribed into antisense RNA that (A) interacts with or (B) recruits multiple negative epigenetic regulators, such as G9A, DNMT3A, and EZH2, to the promoter region of the parental gene to induce an inhibitory effect on its transcription. Some pseudogenes can produce endogenous siRNAs by (C) interacting with sense RNA to form a double-stranded RNA-RNA duplex or (D) being transcribed from the inverted repeat region. Both of these products may undergo Dicer splicing to produce siRNAs, which mediate an RNA interference effect to reduce sense RNA. (E) By containing similar miRNA response elements (MREs) with the miRNA target gene, including the parental gene, pseudogene RNA is capable of competing for miRNAs by serving as a miRNA decoy to enhance expression of miRNA target genes at the posttranscriptional level. (F) Pseudogenes can also generate long noncoding RNAs (lncRNAs) to trigger epigenetic regulations of parental genes; other functions of pseudogene-derived lncRNAs still need to be investigated. (G) Pseudogene RNA is able to compete for RNA-binding proteins (RBPs) with the RNA transcripts of the parental gene. The comprehensive effect on the transcription of the parental gene mainly relies on the subtype of RBP: RNA-stabilizing RBPs and RNA-destabilizing RBPs. Abbreviations: DNMT3A: DNA methyltransferase 3 alpha; EZH2: enhancer of zeste 2 polycomb repressive complex 2 subunit; G9A: euchromatic histone lysine methyltransferase 2; H3K9me3: histone trimethylated at lysine 9; HP1a: Heterochromatin Protein 1A; IRR: inverted repeat region; RBP: RNA binding protein; SUV39H1: suppressor of variegation 3-9 homolog 1.